Furthermore, when β-adrenergic receptor blockade eliminates the positive chronotropic and inotropic effects, activation of the cardiac sympathetic nerves increases coronary resistance. These observations indicate that the direct action of the sympathetic nerve fibers on the coronary resistance vessels is vasoconstriction.
Both α-adrenergic receptors (constrictors) and β2adrenergic receptors (dilators) are present on the coronary vessels. Coronary resistance vessels also participate in the baroreceptor and chemoreceptor reflexes, and the sympathetic constrictor tone of the coronary arterioles can be modulated by such reflexes. Nevertheless, coronary resistance is predominantly under local nonneural control.
Vagus nerve stimulation causes slight dilation of the coronary resistance vessels, and activation of the carotid and aortic chemoreceptors can cause a slight decrease in coronary resistance via the vagus nerves to the heart. Failure of strong vagal stimulation to increase coronary blood flow is not due to lack of muscarinic receptors on the coronary resistance vessels because intracoronary administration of acetylcholine elicits marked vasodilation. In the human heart, acetylcholine caused vasodilation when administered directly into the left anterior descending coronary artery of subjects with no evidence of coronary artery disease. However, acetylcholine caused vasoconstriction in the coronary artery of subjects whose endothelium had been damaged and rendered dysfunctional by atherosclerosis.
A striking characteristic of the coronary circulation is the close relationship between the level of myocardial metabolic activity and the magnitude of coronary blood flow (Fig.
17.33 ). This relationship is also found in a denervated heart and in a completely isolated heart, either in the beating state or in the fibrillating state. Ventricles can fibrillate for many hours when the coronary arteries are perfused with arterial blood from some external source. As already noted, a fibrillating heart uses less O2 than a pumping heart does, and blood flow to the myocardium is reduced accordingly.
The mechanisms that link the cardiac metabolic rate and coronary blood flow remain unsettled. However, it appears that a decrease in the ratio of O2 supply to O2 demand releases vasodilator substances from the myocardial cells into the interstitial fluid, where they relax the coronary resistance vessels. Decreases in arterial blood O2 content or in coronary blood flow and increases in metabolic rate all decrease the O2 supply/demand ratio (
Fig. 17.34 ). As a consequence, substances are released that dilate the arterioles and thereby adjust the O2 supply to the O2 demand. A decrease in O2 demand diminishes the release of vasodilators and enables greater expression of basal tone.
Numerous metabolites participate in the vasodilation that accompanies increased cardiac work. Accumulation of vasoactive metabolites can also account for the increase in blood flow that results from a brief period of ischemia (i.e., reactive hyperemia; see ). The duration of the enhanced coronary flow after release of the briefly occluded vessel is, within certain limits, proportional to the duration of the period of occlusion. Among the factors implicated in reactive hyperemia are ATP-sensitive potassium (KATP) channels, NO, CO2, H+, K+, hypoxia, H2O2, and adenosine.